Insulin receptors and responsiveness have been studied in undifferentiated and fatty 3T3-L1 fibroblasts. The number of receptors in sparse growing cells is low and increases 3-fold when the cells become confluent. With differentiation to fatty phenotypes, receptor number increases another 3-4 fold, without change in affinity. Growing and confluent cells show a small (40%) stimulation of glucose transport and glucose oxidation by insulin, which differentiated cells show a 3-5 fold stimulation. With differentiation increased, sensitivity to insulin is also found. Differentiated cells have spare receptors characteristic of mature adipocytes. Antibody to the insulin receptor initially stimulates glucose transport and oxidation in fatty fibroblasts. This effect disappears after chronic exposure to antibody causing a state of insulin resistance.